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Fisser, MC; Rommer, A; Steinleitner, K; Heller, G; Herbst, F; Wiese, M; Glimm, H; Sill, H; Wieser, R.
Induction of the proapoptotic tumor suppressor gene Cell Adhesion Molecule 1 by chemotherapeutic agents is repressed in therapy resistant acute myeloid leukemia.
Mol Carcinog. 2015; 54(12):1815-1819 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Sill Heinz
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Abstract:
Even though a large proportion of patients with acute myeloid leukemia (AML) achieve a complete remission upon initial therapy, the majority of them eventually relapse with resistant disease. Overexpression of the gene coding for the transcription factor Ecotropic Virus Integration site 1 (EVI1) is associated with rapid disease recurrence and shortened survival. We therefore sought to identify EVI1 target genes that may play a role in chemotherapy resistance using a previously established in vitro model system for EVI1 positive myeloid malignancies. Gene expression microarray analyses uncovered the Cell Adhesion Molecule 1 (CADM1) gene as a candidate whose deregulation by EVI1 may contribute to drug refractoriness. CADM1 is an apoptosis inducing tumor suppressor gene that is inactivated by methylation in a variety of tumor types. In the present study we provide evidence that it may play a role in chemotherapy induced cell death in AML: CADM1 was induced by drugs used in the treatment of AML in a human myeloid cell line and in primary diagnostic AML samples, and its experimental expression in a cell line model increased the proportion of apoptotic cells. CADM1 up-regulation was abolished by ectopic expression of EVI1, and EVI1 expression correlated with increased CADM1 promoter methylation both in a cell line model and in primary AML cells. Finally, CADM1 induction was repressed in primary samples from AML patients at relapse. In summary, these data suggest that failure to up-regulate CADM1 in response to chemotherapeutic drugs may contribute to therapy resistance in AML. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.
Find related publications in this database (using NLM MeSH Indexing)
Aged -
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Apoptosis - genetics
Cell Adhesion Molecule-1 -
Cell Adhesion Molecules - genetics
Cell Line, Tumor -
DNA Methylation - drug effects
DNA Methylation - genetics
DNA-Binding Proteins - genetics
Drug Resistance, Neoplasm - genetics
Female -
Gene Expression - drug effects
Gene Expression - genetics
Genes, Tumor Suppressor - physiology
Humans -
Immunoglobulins - genetics
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
MDS1 and EVI1 Complex Locus Protein -
Middle Aged -
Promoter Regions, Genetic - drug effects
Promoter Regions, Genetic - genetics
Proto-Oncogenes - genetics
Transcription Factors - genetics
Up-Regulation - drug effects
Up-Regulation - genetics

Find related publications in this database (Keywords)
acute myeloid leukemia
chemotherapy resistance
relapse
EVI1
CADM1
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